Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis...

OBJECTIVES: Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use. METHODS: We studied the effects of metformin (Riomet® ) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management...

Second generation antipsychotics (SGA) are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before), clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation...

PURPOSE OF REVIEW: The purpose of this manuscript is to review the evidence generated by clinical trials of pharmaceuticals in autism spectrum disorder (ASD), describe challenges in the conduct of such trials, and discuss future directions RECENT FINDINGS: Clinical trials in ASD have produced several compounds to adequately support the pharmacological treatment of associated symptom domains: attention deficit hyperactivity disorder (methylphenidate, atomoxetine, and alpha agonists), irritability/aggression (risperidone and aripiprazole), sleep (melatonin), and weight gain associated with atypical antipsychotic use (metformin)...

Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on hypothalamic-pituitary-thyroid axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2...

BACKGROUND: Global prescription drug use has been increasing continuously for decades. The gut microbiome, a key contributor to health status, can be altered by prescription drug use, as antibiotics have been repeatedly described to have both short-term and long-standing effects on the intestinal microbiome. AIM: To summarise current findings on non-antibiotic prescription-induced gut microbiome changes, focusing on the most frequently prescribed therapeutic drug categories...

Antipsychotic medications carry an established lifetime risk of metabolic syndrome. This retrospective chart review evaluated feasibility of a metabolic monitoring clinical decision support tool (CDST) for weight, lipid, blood glucose, and blood pressure management of 163 clients in an early psychosis outpatient clinic over 2 years. Each parameter had at least 98 (60.1%) clients with a recorded value, the most being documented for weight with 112 (68.7%) clients. CDST adherence ranged from at least 54.3-100% for non-pharmacologic interventions (e...

OBJECTIVE: A previous study reported on a 16-week placebo-controlled, randomized clinical trial (RCT) of metformin for weight stabilization in 61 children and adolescents 6 to 17 years old with autism spectrum disorder who were prescribed atypical antipsychotics. The present study describes the results of a 16-week open-label extension. METHOD: Fifty-two participants from the acute trial (85%) entered the extension; 22 had been on metformin during the initial RCT and 30 had been on placebo...

Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine...

OBJECTIVES: There is considerable evidence that metformin reduces weight gain associated with antipsychotic medication. The aim of this study was to develop an easy-to-use metformin prescribing tool in order to enable clinicians to prescribe metformin safely and confidently. METHODS: The authors undertook a survey of clinicians and reviewed the published literature and existing guidelines concerning the use of metformin to reduce weight gain in adults with mental illness...

Clozapine has proved to be an effective antipsychotic for the treatment of refractory schizophrenia - characterised by the persistence of symptoms despite optimal treatment trials with at least two different antipsychotics at adequate dose and duration - but its use is hampered by adverse effects. The development of clozapine-induced diabetes is commonly considered to arise as part of a metabolic syndrome, associated with weight gain, and thus evolves slowly. We present the case of an individual with refractory schizophrenia and metformin-controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia immediately after starting clozapine...

BACKGROUND: Patients taking antipsychotic medications are at high risk for weight gain, which in turn leads to poor health outcomes, nonadherence with treatment, and low self-esteem. METHODS: We reviewed published studies of pharmacologic interventions aimed at minimizing antipsychotic-induced weight gain. Treatments initiated prior to onset of weight gain were compared with those that started once weight gain already had occurred. RESULTS: Although data are limited, adjunctive medications for weight management appear to be more effective when initiated at or near the time when patients are first exposed to antipsychotic medications...

Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD...

Metformin, a biguanide drug, is emerging as an important treatment option for the prevention or treatment of weight gain, type 2 diabetes mellitus, and the metabolic syndrome in psychiatric patients, especially those who require or receive antipsychotic drugs. Metformin treatment is commonly associated with gastrointestinal adverse effects; the risk of these is reduced by gradual dose uptitration, administration of the drug with meals, and use of a time-release formulation. Lactic acidosis, a potentially fatal complication of biguanide therapy, is very rare with metformin; the risk can be reduced by avoidance of its prescription in patients with impaired renal function, impaired liver function, cardiac failure, and certain other conditions...